Contribution of Intrinsic Alpha-Motoneuron Excitability to Disuse-Induced Muscle Weakness

内在α运动神经元兴奋性对废用性肌无力的影响

• 批准号: 10294948
• 负责人: Nathan Wages
• 金额: $ 7.05万
• 依托单位: OHIO UNIVERSITY ATHENS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10294948
• 关键词: Activities of Daily Living; Address; Anatomy; Animal Model; Area; Atrophic; Attenuated; Clinical; Computer Models; Computer Simulation; Data; Defect; Development; Educational workshop; Elbow; Elderly; Environment; Evoked Potentials; Fire - disasters; Flexor; Foundations; Frequencies; Goals; Grant; Human; Immobilization; Impairment; Individual; Intervention; Investigation; Knowledge; Link; Magnetism; Manuscripts; Measures; Mechanics; Mediating; Mentorship; Modality; Modeling; Motor; Motor Neurons; Muscle; Muscle Spindles; Muscle Weakness; Muscular Atrophy; Nature; Nerve Degeneration; Nervous system structure; Neurologic; Ohio; Output; Pharmaceutical Preparations; Pharmacology; Physiologic pulse; Physiology; Positioning Attribute; Production; Program Development; Property; Randomized; Reflex action; Research; Research Personnel; Resources; Role; Scientist; Spinal; Students; System; Techniques; Therapeutic Intervention; Training; Universities; Upper arm; Work; base; clinically significant; electric impedance; experimental study; faculty research; functional disability; functional restoration; improved; in vivo; indexing; muscle aging; muscle strength; muscular system; neuromechanism; physically handicapped; post intervention; recruit; sensory input; sex; symposium; technological innovation; tenure track; therapeutically effective; treatment strategy; vibration; young adult

PROJECT SUMMARY/ABSTRACT The work herein, will lay the foundation for a paradigm shift in treatment strategies, focusing on the nervous system, over the muscular system, when addressing physical impairments resulting from immobilization/disuse. The scientific focus on disuse-induced muscle weakness in recent decades has been primarily on muscle wasting (atrophy). Recent longitudinal investigations, and pharmacological drug trials, have clearly demonstrated muscle wasting to be moderately associated with weakness, suggesting a link with an impairment in the neurological system. Research has recently postulated a defect lies in mechanisms specific to the ɑ-motoneuron (MN), which encode repetitive firing. Historically, obtaining valid in vivo indices of human MN excitability has been difficult, but recent technological innovations have afforded scientists this capability. Notably, intrinsic MN excitability can be estimated via paired motor unit analysis (PMUA), and by applying cervicomedullary magnetic stimulation, to elicit a cervicomedullary evoked potential (CMEP). Attenuating muscle weakness, via effective therapeutic interventions, is a clinically significant issue necessitating an in-depth understanding of the spinal mechanism(s) mediating force production. Mechanical (muscle) vibration therapy is well-known to improve force output following prolonged periods of disuse, as vibration activates Ia afferents, which cause slow and fast MNs to increase their respective firing rates via a reflex arc. However, vibration during immobilization is drastically under-utilized as a modality to accelerate the restoration of functional capacity. The PI’s central hypothesis is intrinsic MN hypo-excitability is a key contributor to disuse-induced muscle weakness, while stimulation of Ia afferents is a key contributor to its impedance. In SA 1, the PI will determine if cast-immobilization (a model of disuse) decreases MN excitability. His hypothesis is immobilization will decrease ΔF and CMEP amplitude. In SA 2, the PI will determine if muscle vibration during immobilization restores MN excitability. His hypothesis is vibration will restore ΔF and CMEP amplitude. In SA 3, the PI will use data from SA 1 and 2 to determine how much of the change in force output after immobilization is due to changes in firing of slow vs. fast MNs via computer modeling. His hypotheses are: 1) fast MNs’ firing rate will decrease more significantly than that of slow MNs after immobilization, and 2) vibration will counteract intrinsic MN hypo-excitability by exciting slow and fast MNs to enhance their firing rates. The PI’s training plan will utilize “hands-on” computer simulation via animal models at Wright State University (WSU), significant computer modeling coursework at Ohio University (OU) and WSU, a Professional Development Program at Ohio State University, grantsmanship training/workshops, podium presentations at (inter)national conferences, manuscript compositions/submissions, grant/lab budgetary training, and student mentorship. The physical resources and the intellectual/institutional support available at WSU and OU, will not only provide an excellent environment for the PI to succeed in accomplishing the goals of this study, but will provide the PI with the initial steps in obtaining a tenure-track junior faculty research position.

项目总结/文摘